Conversion surgery for gastric remnant cancer with liver metastasis after nivolumab combination chemotherapy achieving pathological complete response: a case report and literature review.

BACKGROUND: Nivolumab combination chemotherapy has recently emerged as a potential first-line treatment for patients with unresectable or metastatic gastric cancer (GC). Further research has indicated that R0 resection by conversion surgery could be an effective treatment strategy to improve overall survival. However, there have been limited reports on the successful application of conversion surgery following combination chemotherapy achieving pathological complete response (pCR) in cases of advanced gastric remnant cancer with liver metastasis. Here, we present a case of long-term survival in a patient who underwent this treatment. CASE PRESENTATION: A 54-year-old man was initially referred to our department for treatment of stage III (cT3N1M0) gastric cancer where he underwent laparoscopic distal gastrectomy and D2 lymph node dissection. After a year of uneventful follow-up, the patient was diagnosed with a tumor in the gastric remnant combined with liver metastasis, resulting in a diagnosis of stage IV (cT3N0M1) gastric remnant cancer. Subsequently, the patient was treated with four cycles of TS-1, Oxaliplatin, and Nivolumab as the first-line regimen. Remarkably, both the remnant tumor and liver metastasis exhibited significant shrinkage, and no new lesions were found. Given this response, conversion surgery was performed to achieve complete resection of the remnant gastric cancer and liver metastasis, followed by laparoscopic remnant gastrectomy and partial hepatectomy. Pathological examination revealed the absence of residual carcinoma cells and lymph node metastases. Postoperatively, the patient was treated with adjuvant chemotherapy with S-1 for 1 year, and survived without recurrence for 18 months after conversion surgery. CONCLUSIONS: Nivolumab combination chemotherapy shows promise as a clinically beneficial treatment approach for gastric remnant cancer with liver metastasis, particularly when pCR can be achieved following conversion surgery.

Identifying the Trends of Urinary microRNAs within Extracellular Vesicles for Esophageal Cancer.

Background: The advancement of multidisciplinary treatment has increased the need to develop tests to monitor tumor burden during treatment. We herein analyzed urinary microRNAs within extracellular vesicles from patients with esophageal squamous cell carcinoma (ESCC) and normal individuals using a microarray. Methods: Patients with advanced ESCC who underwent esophagectomy (A), endoscopic submucosal resection (ESD) (B), and healthy donors (C) were included. Based on microRNA expression among the groups (Analysis 1), microRNAs with significant differences between groups A and C were selected (Analysis 2). Of these candidates, microRNAs in which the change between A and C was consistent with the change between B and C were selected for downstream analysis (Analysis 3). Finally, microRNA expression was validated in patients with recurrence from A (exploratory analysis). Results: For analysis 1, 205 microRNAs were selected. For Analyses 2 and 3, the changes in 18 microRNAs were consistent with changes in tumor burden as determined by clinical imaging and pathological findings. The AUC for the detection of ESCC using 18 microRNAs was 0.72. In exploratory analysis, three of eighteen microRNAs exhibited a concordant trend with recurrence. Conclusions: The current study identified the urinary microRNAs which were significantly expressed in ESCC patients. Validation study is warranted to evaluate whether these microRNAs could reflect tumor burden during multidisciplinary treatment for ESCC.

Remnant gastritis in gastric cancer patients causes loss of muscle mass 6 months after gastrectomy: a retrospective cohort study of Helicobacter pylori infection.

PURPOSE: In this study, we assessed the relationship between remnant gastritis and muscle mass loss and then investigated the potential relationship between Helicobacter pylori (HP) infection and remnant gastritis and muscle loss. METHODS: We reviewed the medical records of 463 patients who underwent distal gastrectomy between January 2017 and March 2020. Of these patients, 100 with pStage I after laparoscopic surgery were included in this analysis. RESULTS: A multivariate analysis showed that the total Residue, Gastritis, Bile (RGB) classification score, which indicates the degree of gastritis, was significantly associated with the rate of change (rate of decrease) in the psoas muscle area (PMA) during the first 6 months after surgery (p = 0.014). Propensity score matching was performed according to HP infection, and the rate of change in the PMA and the degree of remnant gastritis in 56 patients were compared. Neither was significantly associated with HP infection. CONCLUSIONS: Remnant gastritis did contribute to psoas muscle mass loss during the initial 6 months after gastrectomy, and HP infection was not significantly associated with either remnant gastritis or psoas muscle mass loss. Nevertheless, the potential for HP eradication to prevent muscle loss and improve the survival prognosis for gastrectomy patients merits further research.

Tumor Burden Monitoring with Circulating Tumor DNA During Treatment in Patients with Esophageal Squamous Cell Carcinoma.

BACKGROUND: To guide appropriate treatment strategy, an accurate tumor monitoring modality that reflects tumor burden during neoadjuvant treatment is required for esophageal squamous cell carcinoma (ESCC). We aimed to investigate the clinical utility of circulating tumor DNA (ctDNA) in plasma in patients who received neoadjuvant chemotherapy (NAC) followed by esophagectomy. PATIENTS AND METHODS: Longitudinally collected plasma samples for ctDNA combined with genomic DNA from primary lesions were obtained from patients with histologically confirmed ESCC who underwent NAC followed by subtotal esophagectomy. Next-generation sequencing was performed to identify mutations from the plasma and the primary tumor. The relationships between changes in ctDNA and the pathological response and recurrence were assessed in patients with locally advanced ESCC. RESULTS: In pretreatment samples from 13 patients, multiple concordant mutations in ctDNA and primary tumors were observed in 11 patients (85%), who were classified as ctDNA positive before treatment. The ctDNA positive rate after NAC correlated with the pathological response (responders, 25%; nonresponders, 100%; p = 0.007). The risk of recurrence increased significantly in patients with positive ctDNA after surgery in analysis of 16 patients; the 1-year recurrence-free survival rates were 90 and 0% in ctDNA-negative and ctDNA-positive groups, respectively (p = 0.0008). In two patients with postoperative recurrence, ctDNA was detected approximately 5.5 months earlier than the diagnosis using radiographical imaging. CONCLUSIONS: ctDNA is a promising biomarker for predicting pathological response and postoperative recurrence in ESCC. To demonstrate the external validity, we are currently preparing a multicenter prospective study.

Predictors of sedation period for critical illness patients focusing on early rehabilitation on the bed.

There are various interventions of rehabilitation on the bed, but these are time-consuming and cannot be performed for all patients. The purpose of this study was to identify the patients who require early mobilization based on the level of sedation. We retrospectively evaluated the data of patients who underwent physical therapy, ICU admission of > 48 h, and were discharged alive. Sedation was defined as using sedative drugs and a Richmond Agitation-Sedation Scale score of < - 2. Multiple regression analysis was performed using sedation period as the objective variable, and receiver operating characteristic (ROC) curve and Spearman's rank correlation coefficient were performed. Of 462 patients admitted to the ICU, the data of 138 patients were analyzed. The Sequential Organ Failure Assessment (SOFA) score and non-surgery and emergency surgery cases were extracted as significant factors. The ROC curve with a positive sedation period of more than 3 days revealed the SOFA cutoff score was 10. A significant positive correlation was found between sedation period and the initial day on early mobilization. High SOFA scores, non-surgery and emergency surgery cases may be indicators of early mobilization on the bed in the ICU.

Impact of loss of skeletal muscle mass within 6-12 months after gastrectomy and S1 adjuvant chemotherapy on the survival prognosis of elderly patients with gastric cancer.

BACKGROUND AND PURPOSE: We investigated the impact of postoperative changes in the psoas muscle mass index (PMI) after gastrectomy and S1 adjuvant chemotherapy (AC) on the long-term outcomes of elderly patients with gastric cancer. METHODS: We reviewed the medical records of 228 patients aged over 75 years, who underwent distal, proximal, or total gastrectomy between January, 2013 and March 2017. Among these patients, 78 with pStage IIA-IIIC who survived for at least 1 year without recurrence after gastrectomy were the subjects of this analysis. RESULTS: The log-rank test using the cut-off value from the rate of change in PMI from 6 to 12 months after gastrectomy (late rate of decrease) showed significantly poorer prognosis for the group above the cut-off value for both overall survival (OS) and recurrence-free survival (RFS) (RFS: PMI decrease ≥ 1.55%, p < 0.001; OS: PMI decrease ≥ 1.55%, p < 0.001). Patients with a relative dose intensity of S1 below 68.7% and a late rate of decrease in PMI above 1.55% were found to have a poor prognosis. CONCLUSION: It is necessary to prevent decline in the PMI of elderly patients from 6 months after gastrectomy and to administer adjuvant chemotherapy with about two-thirds or more RDI of S1 to improve their survival prognosis.

Impact of the first era of the coronavirus disease 2019 pandemic on gastric cancer patients: a single-institutional analysis in Japan.

BACKGROUND: Little is known about the disadvantages of the coronavirus disease 2019 (COVID-19) pandemic in patients with gastric cancer. This study aimed to examine the negative impact of the COVID-19 pandemic on patients with gastric cancer in the first era in Japan. METHODS: This retrospective study included 725 patients diagnosed with gastric cancer who visited our hospital between April 2019 and March 2021. The number of patients and their characteristics before and during the COVID-19 pandemic were compared. RESULTS: The number of patients diagnosed with gastric cancer during the COVID-19 pandemic decreased by 26.2% (from 417 to 308; p = 0.013) compared to that before the COVID-19 pandemic. There was a significant decrease in cStage I cancer and an increase in cStage III cancer (p = 0.004). Patients were often symptomatic (p = 0.029), especially those with stenosis-related symptoms (p < 0.001) and longer symptom duration (p < 0.001). The number of endoscopic resections was decreased by 34.8% (p = 0.005). The number of total gastrectomy was higher than that of partial gastrectomy (p = 0.021). The median time to treatment was significantly shorter (p < 0.001). CONCLUSIONS: In Japan, delays diagnosing patients with gastric cancer, probably due to refraining from consultation, may have resulted in an increase in the diagnosis of advanced-stage cancer. Moreover, an increasing proportion of patients required more invasive gastrectomy. Therefore, it may be necessary to educate patients not to refrain from consultation, even during the COVID-19 pandemic, as it can have a negative impact on treatment, policy decision, and prognosis of gastric cancer.

Short-term outcomes of robot-assisted minimally invasive esophagectomy with extended lymphadenectomy for esophageal cancer compared with video-assisted minimally invasive esophagectomy: A single-center retrospective study.

BACKGROUND: The safety and feasibility of robot-assisted minimally invasive esophagectomy (RAMIE) remain unclear. The aim of this study was to compare the short-term outcomes of RAMIE with extended lymphadenectomy and conventional minimally invasive esophagectomy (MIE) in order to investigate the safety and feasibility of RAMIE. METHODS: A retrospective analysis of 87 patients who underwent minimally invasive esophagectomy at our institution between April 2018 and March 2020 was made, assigning 22 in the RAMIE group and 65 in the MIE group. Short-term clinical outcomes and clinical baseline data were compared. RESULTS: The baseline characteristics were comparable. No significant difference in median thoracic phase blood loss and median number of dissected mediastinal lymph nodes were observed. The median operative time of thoracic approach was significantly longer in the RAMIE group than the MIE group (305 minutes [221-397] vs 227 minutes [133-365], P < .0001). With respect to postoperative complications such as recurrent laryngeal nerve paralysis (Clavien-Dindo ≥ grade II) (RAMIE 4.6% vs MIE 17%, P = .11) and postoperative pneumonia (Clavien-Dindo ≥ grade III) (RAMIE 9% vs MIE 23%, P = .13), no significant difference was observed. The patients in the RAMIE group had a better postoperative swallowing function (P = .023) and were able to start oral food intake significantly earlier (P = .007). The median hospital stay was significantly shorter in the RAMIE group than in the MIE (23 days vs 35 days, P = .009). CONCLUSIONS: RAMIE with extended lymphadenectomy was safe and feasible for esophageal cancer and resulted in improved postoperative swallowing function and shorter postoperative hospital stay.

Determining Factors for Independent Walking in Patients Undergoing Cardiovascular Surgery: Differences between Coronary Artery Bypass Grafting, Heart Valve Surgery, and Aortic Surgery.

Physical deconditioning often occurs during the acute phase after cardiovascular surgery, and unassisted walking is required to achieve independence, to manage cardiac diseases, and to prevent recurrences. This study aims to investigate the characteristics of independent walking after cardiovascular surgery. We conducted a retrospective cohort study in patients who underwent cardiovascular surgeries (total of 567 patients): 153 in the coronary artery bypass grafting (CABG) group, 312 in the heart valve surgery group, and 102 in the aortic surgery group. We evaluated the effect of each surgery group on the cardiac rehabilitation (CR) progression. The factors associated with independent walking were age, renal diseases, intensive care unit (ICU) length of stay, and post-operative respiratory complications in the CABG group. In the heart valve surgery group, the factors were New York Heart Association functional classification, renal and respiratory diseases, ICU length of stay, duration of mechanical ventilatory support, and post-operative cardiovascular and respiratory complications. In the aortic surgery group, these were ICU length of stay and acute kidney injury. The CR progression in patients who underwent aortic surgery was significantly longer than those who underwent CABG and heart valve surgery (p < 0.001). New intervention strategies are needed for patients with prolonged ICU stays.

Impact of sarcopenia on the progress of cardiac rehabilitation and discharge destination after cardiovascular surgery.

[Purpose] To investigate the factors that affect the progress of cardiac rehabilitation, length of stay in the hospital, and discharge destination after cardiovascular surgery. [Participants and Methods] This was a prospective observational study. Sixty-seven patients scheduled to undergo open-heart surgery were included in the study. We evaluated physical and psychiatric functions pre- and post-surgery. Sarcopenia was defined as a short physical performance battery score of <9.5. [Results] Sarcopenia was a significant factor of delay of the day of the first rehabilitation, independence in 100-m walking, and exercise training at the rehabilitation gym. Comparisons between pre- and post-surgery were performed in the sarcopenia group. No significant decreases in physical and psychiatric functions were found. The discharge transfer rate was significantly different between the sarcopenia and non-sarcopenia groups. Sarcopenia and the decline in balance score significantly correlated with discharge transfer. [Conclusion] Cardiac rehabilitation can achieve recovery of physical and psychiatric functions even in patients with sarcopenia; however, the discharge transfer rate among the patients with sarcopenia was high. Improving balance ability may result in early home discharge.

Rehabilitation progress after lower-extremity bypass surgery in patients with peripheral arterial disease with different occlusive lesions.

[Purpose] To examine the differences in rehabilitation progress after lower-extremity bypass surgery for peripheral arterial disease (PAD) depending on the occlusive lesions. [Participants and Methods] This was a retrospective study. We included 50 patients (61 limbs; 38 males and 12 females; mean age, 73 years) who underwent lower-extremity bypass surgery for Fontaine stage 2-3 PAD. The patients were assigned to the aortoiliac (A-I) group (n=23), femoropopliteal (F-P) group (n=18), and below-knee group (n=9). We evaluated the postoperative rehabilitation progress and length of hospital stay of these groups. [Results] The postoperative ankle-brachial pressure index (ABI) of the A-I group was significantly lower than that of the F-P group, although there were no differences before surgery. The progress of rehabilitation and the length of hospitalization showed no significant differences among the three groups. The postoperative date of independent walking was significantly later in the presence of complications than in the absence of complications. [Conclusion] The progress of rehabilitation after lower-extremity bypass surgery did not differ depending on the occlusive lesions, and patients may acquire independent walking ability in approximately 5 days in the absence of postoperative complications.

Performance of a deep learning-based identification system for esophageal cancer from CT images.

BACKGROUND: Because cancers of hollow organs such as the esophagus are hard to detect even by the expert physician, it is important to establish diagnostic systems to support physicians and increase the accuracy of diagnosis. In recent years, deep learning-based artificial intelligence (AI) technology has been employed for medical image recognition. However, no optimal CT diagnostic system employing deep learning technology has been attempted and established for esophageal cancer so far. PURPOSE: To establish an AI-based diagnostic system for esophageal cancer from CT images. MATERIALS AND METHODS: In this single-center, retrospective cohort study, 457 patients with primary esophageal cancer referred to our division between 2005 and 2018 were enrolled. We fine-tuned VGG16, an image recognition model of deep learning convolutional neural network (CNN), for the detection of esophageal cancer. We evaluated the diagnostic accuracy of the CNN using a test data set including 46 cancerous CT images and 100 non-cancerous images and compared it to that of two radiologists. RESULTS: Pre-treatment esophageal cancer stages of the patients included in the test data set were clinical T1 (12 patients), clinical T2 (9 patients), clinical T3 (20 patients), and clinical T4 (5 patients). The CNN-based system showed a diagnostic accuracy of 84.2%, F value of 0.742, sensitivity of 71.7%, and specificity of 90.0%. CONCLUSIONS: Our AI-based diagnostic system succeeded in detecting esophageal cancer with high accuracy. More training with vast datasets collected from multiples centers would lead to even higher diagnostic accuracy and aid better decision making.

Association of lower extremity function with nutritional status and number of drugs in patients with chronic heart failure.

OBJECTIVE: This study was performed to investigate the physical performance parameters, including lower extremity function parameters, that may be risk factors for falls in patients with chronic heart failure. METHODS: Seventy patients with stable chronic heart failure were included in this retrospective cross-sectional study. The five-repetition sit-to-stand test (5STS) time, Controlling Nutritional Status (CONUT) score, and number of drugs were assessed. RESULTS: Simple linear regression analysis revealed that the 5STS time was positively correlated with age, the CONUT score, and the number of drugs but was negatively associated with the handgrip force, quadriceps force, and quadriceps muscle thickness. Multiple linear regression analysis showed a significant association between the 5STS time and the CONUT score, quadriceps force, and number of drugs. CONCLUSION: The muscle strength, nutritional status, and number of drugs should be evaluated to prevent lower extremity weakness in patients with stable chronic heart failure.

[Risk Factors for Post-operative Respiratory Failure and Respiratory Tract Infections Following Cardiovascular Surgery].

INTRODUCTION: Respiratory failure and respiratory tract infections are frequently observed as post-operative pulmonary complications, and significantly contribute to morbidity and mortality. However, the risk factors of post-operative respiratory failure and respiratory tract infections are controversial, and how these factors affect on incidence of complications is still unclear. OBJECTIVE: To identify risk factors of post-operative respiratory failure and respiratory tract infections, and evaluate its impact on incidences after cardiovascular surgery. METHODS: From June 2013 to May 2015, adult patients undergoing cardiovascular surgery in the department of cardiovascular surgery and post-operative rehabilitation of Nagasaki University Hospital (Nagasaki, Japan) were retrospectively investigated. RESULTS: Fifty-two of 416 patients(12.5%)suffered from post-operative respiratory failure and respiratory tract infections. Identified risk stratification indicates the relevant operative factors were more important than pre-operative factors. The operative time (OR 1.696, 95% CI 1.302~2.211), post-operative water balance( OR 1.025, 95% CI 1.004~1.046)and emergency operation( OR 3.607, 95% CI 1.492~8.716)were significant independent risk factors in the development of post-operative respiratory failure and respiratory tract infections. CONCLUSIONS: These results indicated that the operative factors are more important as onset of post-operative respiratory failure and respiratory tract infections after cardiovascular surgery.

Incidence of orthostatic hypotension and cardiovascular response to postoperative early mobilization in patients undergoing cardiothoracic and abdominal surgery.

BACKGROUND: In cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery. METHODS: In this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors. RESULTS: OH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis. CONCLUSIONS: These results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized. TRIAL REGISTRATION: University hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632 . (Registered on 1st October, 2008).

Long-term continuous versus intermittent cyclosporin: therapy for psoriasis.

A multicenter randomized controlled study was conducted to assess the long-term efficacy and safety of cyclosporin A therapy for psoriasis using either a continuous or an intermittent regimen. Initially, both regimens consisted of 3-5 mg/kg/day administration of CyA. Once remission was obtained, CyA dose was maintained between 0.5 and 3 mg/kg/day under the continuous regimen, while under the intermittent regimen, CyA dose was tapered off and, when necessary, topical corticosteroids were used until relapse occurred. Thirty-one patients were followed for at least 48 months (mean follow-up period: 55.9+/-4.6 months): 15 received continuous therapy, and 16 received intermittent therapy. With both regimens, the PASI (Psoriasis Area and Severity Index) score was maintained at 5-12 points throughout the follow-up period. The score was decreased by more than 70% from baseline with both regimens: the responses between them were not significantly different. However, overall control of psoriasis, as assessed from the averaged PASI score, was better in the patients receiving continuous therapy. Although the overall frequency of adverse reactions was similar for the two regimens, cancer occurred in two patients on continuous therapy (gastric cancer and hepatocellular carcinoma in one patient each). We could not, however, definitely attribute the cancers in the two patients to continuous therapy itself. There was a significantly higher incidence of renal impairment in elderly patients receiving either regimen when compared with younger patients. In conclusion, CyA administered to psoriasis patients under both regimens exhibited long-term efficacy and tolerability. Despite a lower overall efficacy, it seems proper to conclude that intermittent therapy is more useful than continuous therapy due to the occurrence of malignancies with continuous therapy. Further investigation is required to determine whether intermittent therapy is really safer than continuous therapy, and, if so, how it should be designed to minimize long-term adverse reactions and achieve overall control comparable to that of continuous CyA therapy.